Mathematic Modeling Of The Biochemical Process For Preparing Two Kinds Of Antibiotics

The content of this thesis is divided into two parts: the chemical synthesis of tilmicosin and biological synthesis of mildiomycin. The purposes of this research are to optimize the two different processes and to establish corresponding mathematical models to describe the processes.The distribution property of desmycosin between water and butyl acetate is studied in the first step of synthesis. It is found that there were almost the same properties of tylosin derivatives in the aspect of distribution in two different solutions. The main reaction from tylosin to desmycosin belonged to Leuckart reaction in which the formic acid was added as a kind of reducer. The optimal ratio of amyl acetate to desmycosin was about 1.2:1. Further extraction and stripping were needed several times for transporting tilmicosin between aqueous and butyl acetate phases. Result showed that the optimal stripping of tilmicosin was achieved when the pH of water was at 4.5, and pH 11 in the extraction process. The equilibrium time was about 20 min at 200rpm. Two dissociation constants were calculated as 8.60 and 7.37, with real distribution coefficient as 78.99. At the same time the enthalpy of dissociation was -46.3kJ/mol.For mildomycin fermentation, the cultivation media was optimized on the basis of previous study. Three factors were selected among 9 factors by the aid of Plackett-Burman method. Then those 3 factors were further investigated to actualize the best productivity of tilmicosin, which was found to be as follows: corn starch 93.35g L"1, soybean meal 41.8 g L"1, cholinechloridel5.5 mmol L"1. When the fermentation of mildiomycin was in a 10L pilot-scale fermenter, it was found that the dissolved oxygen at 20% of saturation and agitation rate of 500rpm were in favor of fermentation. If the spore solution was used as seed feed instead of mycelium suspention, the production of mildiomycin could be enhanced about 40%. It is also found out that feed solution such as Fe2+ and P could make negligible effect on the production of mildiomycin.According to the growth mechanisms of filamentous microorganisms and the kinetic characters of mildiomycin biosynthesis, a mathematical model was established to simulate the fermentation process. The results demonstrated that the model was able to describe the growth of filamentous microorganisms and the production of second metabolite. Because of the drawback of that model which was too complex to take into practice, a relative simple but despicable model was proposed. Furthermore, the phenomenon of chaos was found in the process ofsimulation which is worth of further investigation.